Ultrasound-modulated optical tomography of absorbing objects buried in dense tissue-simulating turbid media

Continuous-wave ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The buried object had an absorption coefficient greater than the background turbid medium. The ultrasonic wave that was focused into the turbid media modulated the laser light that passed through the ultrasonic field. The modulated laser light that was collected by a photomultiplier tube reflected the local mechanical and optical properties in the zone of ultrasonic modulation. Objects buried in the middle plane of 5-cm-thick dense turbid media were imaged with millimeter resolution through the scanning and detecting alterations of the ultrasound-modulated optical signal. The optical properties of the dense turbid media included an absorption coefficient of 0.1 cm(-1) and a reduced scattering coefficient of 10 cm(-1) and were comparable with those of biological tissues in the visible and near-IR ranges. The dependence of the ultrasound-modulated optical signal on the off-axis distance of the detector from the optic axis and the area of the detector was studied as well.     

Ultrasound-modulated optical tomography of biological tissue by use of contrast of laser speckles

Ultrasound-modulated optical tomography based on the measurement of laser-speckle contrast was investigated. An ultrasonic beam was focused into a biological-tissue sample to modulate the laser light passing through the ultrasonic column inside the tissue. The contrast of the speckle pattern formed by the transmitted light was found to depend on the ultrasonic modulation and could be used for imaging. Variation in the speckle contrast reflected optical inhomogeneity in the tissue. With this technique, two-dimensional images of biological-tissue samples of as much as 25 mm thick were successfully obtained with a low-power laser. The technique was experimentally compared with speckle-contrast-based, purely optical imaging and with parallel-detection imaging techniques, and the advantages over each were demonstrated.     

Signal dependence and noise source in ultrasound-modulated optical tomography

A Monte Carlo modeling technique was used to simulate ultrasound-modulated optical tomography in inhomogeneous scattering media. The contributions from two different modulation mechanisms were included in the simulation. Results indicate that ultrasound-modulated optical signals are much more sensitive to small embedded objects than unmodulated intensity signals. The differences between embedded absorption and scattering objects in the ultrasound-modulated optical signals were compared. The effects of neighboring inhomogeneity and background optical properties on the ultrasound-modulated optical signals were also studied. We analyzed the signal-to-noise ratio in the experiment and found that the major noise source is the speckle noise caused by small particle movement within the biological tissue sample. We studied this effect by incorporating a Brownian motion factor in the simulation.     

Autocorrelation of scattered laser light for ultrasound-modulated optical tomography in dense turbid media

Based on measurement of the intensity autocorrelation function, a new method to determine the modulation depth of scattered laser light modulated by an ultrasonic wave in turbid media was applied to ultrasound-modulated optical tomography. Good signal-to-noise ratios and high sensitivities were demonstrated. Images of double optically absorbing objects buried in a highly optically scattering gel sample were obtained. The contrast was more than 10%, and the spatial resolution was approximately 2 mm.     

Optimal beam size for light delivery to absorption-enhanced tumors buried in biological tissues and effect of multiple-beam delivery: a Monte Carlo study

Optimal laser light delivery into turbid biological tissues was studied by using Monte Carlo simulations based on the delta-scattering technique. The goal was to deliver efficiently the maximum amount of optical power into buried tumors being treated while avoiding potential damage to normal tissue caused by strong optical power deposition underneath the tissue surface illuminated by the laser beam. The buried tumors were considered to have much higher absorption than the surrounding normal tissue because of selective uptake of the absorption-enhancement dye. The power delivering efficiency to buried tumors was investigated for various diameters of the laser beam. An optimal beam diameter was estimated to achieve the maximum product of the power coupling efficiency and the power delivered to the buried tumor. The distribution of power deposition was simulated for single-beam delivery and multiple-beam delivery as well. The simulated results showed that with an appropriate dye enhancement and an optimal laser delivery configuration, a high selectivity for laser treatment of tumor could be achieved.     

Correlation transfer equation for multiply scattered light modulated by an ultrasonic pulse

We develop a temporal correlation transfer equation (CTE) and a Monte Carlo algorithm (MC) for multiply scattered light modulated by an ultrasonic pulse propagating in an optically scattering medium, where the ultrasound field can be nonuniform and the medium can have spatially heterogeneous distribution of optical parameters. The CTE and MC can be used to obtain the time-varying specific intensity and the spatial distribution of the time-dependent power spectral density, respectively, of ultrasound-modulated light. We expect the CTE and MC to be applicable for estimation of contrast and resolution in a wide spectrum of conditions in ultrasound-modulated optical tomography of soft biological tissues.     

Imaging in diffuse media with pulsed-ultrasound-modulated light and the photorefractive effect

Acousto-optic imaging in diffuse media is a dual wave-sensing technique in which an acoustic field interacts with multiply scattered laser light. The acoustic field causes a phase modulation in the optical field emanating from the interaction region, and this phase-modulated optical field carries with it information about the local optomechanical properties of the media. We report on the use of a pulsed ultrasound transducer to modulate the optical field and the use of a photorefractive-crystal-based interferometry system to detect ultrasound-modulated light. The use of short pulses of focused ultrasound allows for a one-dimensional acousto-optic image to be obtained along the transducer axis from a single, time-averaged acousto-optic signal. The axial and lateral resolutions of the system are controlled by the spatial pulse length and width of the ultrasound beam, respectively. In addition, scanning the ultrasound transducer in one dimension yields two-dimensional images of optical inhomogeneities buried in turbid media.     

Methods for parallel-detection-based ultrasound-modulated optical tomography

The research reported here focuses on ultrasound-modulated optical tomography based on parallel speckle detection. Four methods were investigated for signal acquisition and analysis, in which laser speckle statistics was applied. The methods were compared with the previously used four-phase method in the imaging of all-biological-tissue samples, in which the buried objects were also biological tissues. The image quality obtained with these methods was comparable with that obtained with the four-phase method; in addition, these methods have advantages in reducing acquisition time and improving the signal-to-noise ratio.     

Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue

The absorption and transport scattering coefficients of biological tissues determine the radial dependence of the diffuse reflectance that is due to a point source. A system is described for making remote measurements of spatially resolved absolute diffuse reflectance and hence noninvasive, noncontact estimates of the tissue optical properties. The system incorporated a laser source and a CCD camera. Deflection of the incident beam into the camera allowed characterization of the source for absolute reflectance measurements. It is shown that an often used solution of the diffusion equation cannot be applied for these measurements. Instead, a neural network, trained on the results of Monte Carlo simulations, was used to estimate the absorption and scattering coefficients from the reflectance data. Tests on tissue-simulating phantoms with transport scattering coefficients between 0.5 and 2.0 mm(-1) and absorption coefficients between 0.002 and 0.1 mm(-1) showed the rms errors of this technique to be 2.6% for the transport scattering coefficient and 14% for the absorption coefficients. The optical properties of bovine muscle, adipose, and liver tissue, as well as chicken muscle (breast), were also measured ex vivo at 633 and 751 nm. For muscle tissue it was found that the Monte Carlo simulation did not agree with experimental measurements of reflectance at distances less than 2 mm from the incident beam.     

Three-dimensional acousto-optic imaging in biological tissues with parallel signal processing

An original acousto-optic method is described that allows one to reveal optical contrasts through biological tissues that are several centimeters thick with a millimeter-sized resolution. This technique is based on the interaction of scattered laser light with a focused ultrasonic field. The modulation depth of the optical speckle is related to local optical properties of the sample. Our parallel-processing approach to the demodulation of the speckle improves the observed degree of modulation by 2 orders of magnitude and quickly yields a good statistical value. Optically absorbing objects were imaged inside 35-mm-thick biological tissues.     

Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm

Fiber-optic probes are widely used in optical spectroscopy of biological tissues and other turbid media. Only limited information exists, however, on the ways in which the illumination-collection geometry and the overall probe design influence the interrogation of media. We have investigated both experimentally and computationally the effect of probe-to-target distance (PTD) on the diffuse reflectance collected from an isotropically (Lambertian) scattering target and an agar-based tissue phantom. Studies were conducted with three probes characterized by either common (single-fiber) or separate (two bifurcated multifiber probes) illumination and collection channels. This study demonstrates that PTD, probe design, and tissue scattering anisotropy influence the extent of the transport of light into the medium, the light-collection efficiency, and the sampling volume of collected light. The findings can be applied toward optimization of fiber-optic probe designs for quantitative optical spectroscopy of turbid media including biological tissues.     

Toward virtual biopsy through an all fiber optic ultrasonic miniaturized transducer: a proposal

The present generation of devices based on opto-acoustic and acousto-optic conversion lets us foresee the possibility of realizing complete miniaturized transmitting-receiving transducers, able to generate and detect wideband ultrasounds by laser light. In the present paper, a miniaturized ultrasonic transducer entirely based on fiber optic technology is proposed. Such a device springs from the conjunction between our research, which has produced a highly efficient fiber optic opto-acoustic source, with the results obtained by other researchers concerning the realization of an ultrasonic receiver based on optical interferometry. Making use of the thermo-elastic effect for ultrasound generation, a source of ultrasound can be obtained by coupling a fiber optic to pulsed laser, if a film capable of absorbing laser light is placed onto fiber end. Starting from these remarks, we propose an efficient opto-acoustic source, able to generate pressure pulses with amplitude of the order of 10(4) Pa and bandwidth extending up to 40 MHz and beyond by using graphite materials as absorbing film. This solution makes use of a low-power pulsed laser as optical source possible. An ultrasonic receiving element was realized placing a Fabry-Perot cavity over the tip of a fiber optic. The cavity thickness modulation induced by ultrasonic beam is detected by an interferometer optical technique. We have realized a prototype of a receiving device that exhibits a sensitivity comparable with that of piezoelectric devices (10-100 nV/Pa) and an almost flat bandwidth extending up to 20 MHz or more. The extreme miniaturization of the resulting ultrasonic transducer, together with its wide ultrasonic frequency bandwidth, is the first step toward ultrasonic tissue biopsy. In this paper, before discussing the problem of constructing a complete ultrasonic transducer composed by a transmitter and receiver, the results carried out in these fields during the last decade are reviewed.     

In vivo demonstration of the ultrasound-modulated light technique

We present, to our knowledge for the first time, results of ultrasound-modulated light signals on living tissues. In particular, we analyze, both theoretically and experimentally, the effect of speckle fluctuations on the signal. We find that two different kinds of noise compete--shot noise and speckle noise--and are present at different levels in static phantoms and ex vivo tissue samples on the one hand and in dynamic phantoms and living tissues on the other hand.     

Transmission- and side-detection configurations in ultrasound-modulated optical tomography of thick biological tissues

Ultrasound-modulated optical tomography of thick biological tissues was studied based on speckle-contrast detection. Speckle decorrelation was investigated with biological tissue samples of various thicknesses. Images of optically absorbing objects buried in biological tissue samples with thicknesses up to 50 mm were obtained in a transmission-detection configuration. The image contrast was more than 30%, and the spatial resolution was approximately 2 mm. In addition, a side-detection scheme along with two specific configurations were examined, and the advantages were demonstrated. Experimental results implied feasibility of applying the ultrasound-modulation technique to characterize optical properties in inhomogeneous biological tissues.     

生物声学成像中声速不均匀性解决方法的研究进展

对于以超声波为载体的生物医学声学成像(如超声、光声和磁声成像等)技术,为了简化问题,常在假设待测组织内声速恒定的前提下,重建组织内的声阻抗、光吸收分布、光学特性参数分布或者电导率分布等。但是,实际生物组织内部的声速是存在差异的(最大可达10%),因而在此假设前提下重建出的图像通常是不准确的。在介绍声速不均匀性对声学图像重建影响的基础上,对超声、光声和磁声成像中解决声速不均匀问题的主要方法,特别是光声层析成像中重建组织内声速分布的主要方法进行总结和归纳,讨论各自的优点和不足,并展望未来的可能发展方向。     

Coherent backscattering cone shape depends on the beam size

Coherent backscattering (CBS) is a beautiful physical phenomenon that takes place in a highly scattering medium, which has potential application in noninvasive optical property measurement. The current model that explains the CBS cone shape, however, assumes the incoming beam diameter is infinitely large compared to the transport length. In this paper, we evaluate the effect of a finite scalar light illumination area on the CBS cone, both theoretically and experimentally. The quantitative relationship between laser beam size and the CBS cone shape is established by using two different finite beam models (uniform top hat and Gaussian distribution). A series of experimental data with varying beam diameters is obtained for comparison with the theory. Our study shows the CBS cone shape begins to show distortion when beam size becomes submillimeter, and this effect should not be ignored in general. In biological tissue where a normal large beam CBS cone is too narrow for detection, this small beam CBS may be more advantageous for more accurate and higher resolution tissue characterization.     

Experimental and simulated ultrasonic characterization of complex damage in fused silica

The growth of a laser-induced. surface damage site in a fused silica window was monitored by the ultrasonic pulse-echo technique. The laser damage was grown using 12-ns pulses of 1.053-μm wavelength light at a fluence of ~27 J/cm². The ultrasonic data were acquired after each pulse of the laser beam for 19 pulses. In addition, optical images of the surface and subsurface damage shape were recorded after each pulse of the laser. The ultrasonic signal amplitude exhibited variations with the damage size, which were attributed to the subsurface morphology of the damage site. A mechanism for the observed ultrasonic data based on the interaction of the ultrasound with cracks radiating from the damage site was tested using two-dimensional numerical simulations. The simulated results exhibit qualitatively similar characteristics to the experimental data and demonstrate the usefulness of numerical simulation as an aid for ultrasonic signal interpretation. The observed sensitivity to subsurface morphology makes the ultrasonic methodology a promising tool for monitoring laser damage in large aperture laser optics used in fusion energy research     

A new optical coefficient of biological tissue that determines the diffuse reflectance light distribution on the tissue surface

When a light beam is incident normally upon a tissue, the spatial distribution of diffuse reflectance on the tissue surface is affected by the optical properties of the tissue. The purpose of this paper is to find the relationship between the spatial distribution of diffuse reflectance on the tissue surface and optical properties of the tissue. The diffuse reflected light distribution is found to be determined mainly by a new optical coefficient μ_as. A qualitative relationship between μ_as and the diffuse reflected light distribution was developed by Monte Carlo simulations. Measurements of the diffuse reflected light distribution on solutions of Intralipid-10% with added ink confirm the Monte Carlo simulations. The new optical coefficient μ_as was measured from several tissue examples by the qualitative relationship. The value of μ_as was useful for determining the components of the tissue.     

Depth-resolved two-dimensional stokes vectors of backscattered light and mueller matrices of biological tissue measured with optical coherence tomography

Mueller matrices provide a complete characterization of the optical polarization properties of biological tissue. A polarization-sensitive optical coherence tomography (OCT) system was built and used to investigate the optical polarization properties of biological tissues and other turbid media. The apparent degree of polarization (DOP) of the backscattered light was measured with both liquid and solid scattering samples. The DOP maintains the value of unity within the detectable depth for the solid sample, whereas the DOP decreases with the optical depth for the liquid sample. Two-dimensional depth-resolved images of both the Stokes vectors of the backscattered light and the full Mueller matrices of biological tissue were measured with this system. These polarization measurements revealed some tissue structures that are not perceptible with standard OCT.     

Tomographic image reconstruction from optical projections in light-diffusing media

The recent developments in light generation and detection techniques have opened new possibilities for optical medical imaging, tomography, and diagnosis at tissue penetration depths of ~10 cm. However, because light scattering and diffusion in biological tissue are rather strong, the reconstruction of object images from optical projections needs special attention. We describe a simple reconstruction method for diffuse optical imaging, based on a modified backprojection approach for medical tomography. Specifically, we have modified the standard backprojection method commonly used in x-ray tomographic imaging to include the effects of both the diffusion and the scattering of light and the associated nonlinearities in projection image formation. These modifications are based primarily on the deconvolution of the broadened image by a spatially variant point-spread function that is dependent on the scattering of light in tissue. The spatial dependence of the deconvolution and nonlinearity corrections for the curved propagating ray paths in heterogeneous tissue are handled semiempirically by coordinate transformations. We have applied this method to both theoretical and experimental projections taken by parallel- and fan-beam tomography geometries. The experimental objects were biomedical phantoms with multiple objects, including in vitro animal tissue. The overall results presented demonstrate that image-resolution improvements by nearly an order of magnitude can be obtained. We believe that the tomographic method presented here can provide a basis for rapid, real-time medical monitoring by the use of optical projections. It is expected that such optical tomography techniques can be combined with the optical tissue diagnosis methods based on spectroscopic molecular signatures to result in a versatile optical diagnosis and imaging technology.